The BEXXAR therapeutic regimen is not indicated for the initial treatment of patients with CD20 positive non-Hodgkin’s lymphoma. (See ADVERSE REACTIONS, Immunogenicity.)

The BEXXAR therapeutic regimen is intended as a single course of treatment. The safety of multiple courses of the BEXXAR therapeutic regimen, or combination of this regimen with other forms of irradiation or chemotherapy, has not been eva luated.

CONTRAINDICATIONS
The BEXXAR therapeutic regimen is contraindicated in patients with known hypersensitivity to murine proteins or any other component of the BEXXAR therapeutic regimen.

PREGNANCY CATEGORY X
Iodine I 131 Tositumomab (a component of the BEXXAR therapeutic regimen) is contraindicated for use in women who are pregnant. Iodine-131 may cause harm to the fetal thyroid gland when administered to pregnant women. Review of the literature has shown that transplacental passage of radioiodide may cause severe, and possibly irreversible, hypothyroidism in neonates. While there are no adequate and well-controlled studies of the BEXXAR therapeutic regimen in pregnant animals or humans, use of the BEXXAR therapeutic regimen in women of childbearing age should be deferred until the possibility of pregnancy has been ruled out. If the patient becomes pregnant while being treated with the BEXXAR therapeutic regimen, the patient should be apprised of the potential hazard to the fetus (see BOXED WARNING, Pregnancy Category X).

WARNINGS

Prolonged and Severe Cytopenias (see BOXED WARNINGS; ADVERSE REACTIONS, Hematologic Events)
The most common adverse reactions associated with the BEXXAR therapeutic regimen were severe or life-threatening cytopenias (NCI CTC grade 3 or 4) with 71% of the 230 patients enrolled in clinical studies experiencing grade 3 or 4 cytopenias. These consisted primarily of grade 3 or 4 thrombocytopenia (53%) and grade 3 or 4 neutropenia (63%). The time to nadir was 4 to 7 weeks and the duration of cytopenias was approximately 30 days. Thrombocytopenia, neutropenia, and anemia persisted for more than 90 days following administration of the BEXXAR therapeutic regimen in 16 (7%), 15 (7%), and 12 (5%) patients respectively (this includes patients with transient recovery followed by recurrent cytopenia). Due to the variable nature in the onset of cytopenias, complete blood counts should be obtained weekly for 10-12 weeks. The sequelae of severe cytopenias were commonly observed in the clinical studies and included infections (45% of patients), hemorrhage (12%), a requirement for growth factors (12% G- or GM-CSF; 7% Epoetin alfa) and blood product support (15% platelet transfusions; 16% red blood cell transfusions). Prolonged cytopenias may also influence subsequent treatment decisions.

The safety of the BEXXAR therapeutic regimen has not been established in patients with >25% lymphoma marrow involvement, platelet count<100,000 cells/mm3 or neutrophil count <1,500 cells/mm3.

Hypersensitivity Reactions Including Anaphylaxis (see BOXED WARNINGS; ADVERSE REACTIONS, Hypersensitivity Reactions and Immunogenicity)
Serious hypersensitivity reactions, including some with fatal outcome, were reported during and following adminis